We develop new treatments for infectious diseases to limit the use of broad-spectrum antibiotics. Microbial infections of the gut do not respond well to conventional drugs, which wreak havoc to the gut microbiome. While experimental methods such as faecal transplants gain traction, they often give unpredictable outcomes. To manipulate the microbiome in a more precise manner, we turned our attention to the peptide antibiotics produced by enteric bacteria, microcins. Microcins can control microbial competition in the gut and restrict growth of pathogenic bacteria. Many microcins belong to the ribosomally synthesized post-translationally modified peptide (RiPP) group. RiPP biosynthesis is guided by a leader peptide that is used to attract and bind biosynthetic machinery that converts the following ‘core’ peptide into a bioactive molecule. RiPPs might contain numerous modifications, and in this project, we will focus on a specific, but a very widespread one: introduction of thiazole and oxazole rings formed from serine and cysteine residues of a precursor peptide.
This project will be a collaboration between the groups of Dmitry Ghilarov and Andrew Truman at the John Innes Centre and Falk Hildebrand of the Quadram Institute Bioscience. The aim is to investigate the diversity of thiazole/oxazole-containing microcins in the human gut microbiome by metagenome analysis and use this knowledge to discover and design new therapeutic peptides.
The successful candidate will be part of an interdisciplinary team focussed on antibiotic discovery and resistance and will have the opportunity to steer the direction of their research. The project provides an exceptional training opportunity in bioinformatics including metagenome assembly and analysis, molecular microbiology, protein and natural product purification and structural biology, including cryo-EM. The successful candidate also will be supported in acquiring transferable skills such as written and spoken communication, problem solving and critical thinking and will help to train undergraduate and visiting students.
The Microbes, Microbiomes and Bioinformatics (MMB) Doctoral Training Partnership (DTP) is open to UK and international candidates with relevant undergraduate degrees for entry in October 2023 and offers the opportunity to undertake a 4-year PhD research project funded by the UKRI Medical Research Council in microbiology and microbial bioinformatics.
Our unique and comprehensive training programme empowers students to feel comfortable running sophisticated computer analyses alongside laboratory work and emphasises problem-based learning in microbial bioinformatics, professional development and research skills. All students will undertake a Professional Placement.
Interviews for shortlisted candidates will take place on Wednesday 15 February or Tuesday 16 February 2023.
The MRC DTP is committed to equality, diversity and inclusion. Students are selected without regard to age, disability, gender identity, marriage or civil partnership, pregnancy or maternity, ethnicity, religion or belief, sex or sexual orientation or social background. We value curiosity, independence of thought, plus an aptitude for research that combines laboratory work and bioinformatics.
For information on eligibility and how to apply: www.uea.ac.uk/phd/mmbdtp